The present invention predominantly deals with non-invasive determination of attributes in humans or human samples by quantitative spectroscopy. Spectroscopy offers the potential of completely non-invasive measurements for a variety of applications such as alcohol monitoring, glucose monitoring, diagnostic medicine, quality control, and process monitoring. Non-invasive measurements that use quantitative spectroscopy are desirable because they are painless, do not require a fluid draw from the body, carry little risk of contamination or infection, do not generate any hazardous waste, and can have short measurement times. Quantitative spectroscopy can measure a variety of attributes of interest including, as examples, analyte presence, analyte concentration (e.g., alcohol or substance of abuse concentration), direction of change of an analyte concentration, rate of change of an analyte concentration, disease presence (e.g., alcoholism or diabetes), disease state, and combinations and subsets thereof.
Several approaches have been proposed for the non-invasive determination of attributes in humans or human samples. These systems have included technologies incorporating polarimetry, mid-infrared spectroscopy, Raman spectroscopy, Kromoscopy, fluorescence spectroscopy, nuclear magnetic resonance spectroscopy, radio-frequency spectroscopy, ultrasound, transdermal measurements, photo-acoustic spectroscopy, and near-infrared spectroscopy. Many of these approaches share a common need to deliver light to and collect light from the sample of interest. The sample of interest can be skin tissue of a subject, biopsied tissue, internal tissues accessed by an endoscope, blood, saliva, urine, or any other biological tissue of interest. In the context of non-invasive measurements, the part of a system that delivers and collects the light is often referred to as an optical probe or an optical sampler. One skilled in the art recognizes that other terms may exist that refer to a system component that serves this purpose.
Many systems for non-invasive measurement of analytes are known in the art, several of which describe embodiments of optical probes for measuring analytes in biological samples. As an example, Robinson et al. in U.S. Pat. No. 4,975,581 disclose a method and apparatus for measuring a characteristic of unknown value in a biological sample using infrared spectroscopy in conjunction with a multivariate model that is empirically derived from a set of spectra of biological samples of known characteristic values. The above-mentioned characteristic is generally the concentration of an analyte, such as alcohol, but also can be any chemical or physical property of the sample. The method of Robinson et al. involves a two-step process that includes both calibration and prediction steps.
In the calibration step, the infrared light is coupled to calibration samples of known characteristic values so that there is attenuation of at least several wavelengths of the infrared radiation as a function of the various components and analytes comprising the sample with known characteristic value. The infrared light is coupled to the sample by passing the light through the sample or by reflecting the light off the sample. Absorption of the infrared light by the sample causes intensity variations of the light that are a function of the wavelength of the light. The resulting intensity variations at a minimum of several wavelengths are measured for the set of calibration samples of known characteristic values. Original or transformed intensity variations are then empirically related to the known characteristics of the calibration samples using multivariate algorithms to obtain a multivariate calibration model.
In the prediction step, the infrared light is coupled to a sample of unknown characteristic value, and a multivariate calibration model is applied to the original or transformed intensity variations of the appropriate wavelengths of light measured from this unknown sample. The result of the prediction step is the estimated value of the characteristic of the unknown sample. The disclosure of Robinson et al. is incorporated herein by reference.
A further method of building a calibration model and using such model for prediction of analytes and/or attributes of tissue is disclosed in commonly assigned U.S. Pat. No. 6,157,041 to Thomas et al., entitled “Method and Apparatus for Tailoring Spectrographic Calibration Models,” the disclosure of which is incorporated herein by reference.
In U.S. Pat. No. 5,830,112, Robinson describes a general method of robust sampling of tissue for non-invasive analyte measurement. The sampling method utilizes a tissue-sampling accessory that is pathlength optimized by spectral region for measuring an analyte such as alcohol. The patent discloses several types of spectrometers for measuring the spectrum of the tissue from 400 to 2500 nm, including acousto-optical tunable filters, discrete wavelength spectrometers, filters, grating spectrometers and FTIR spectrometers. The disclosure of Robinson is incorporated hereby reference.
Although there has been substantial work conducted in attempting to produce commercially viable non-invasive spectroscopy-based systems for determination of attributes in humans and human samples, several challenges remain. It is believed that the systems described in the prior art have had limited success because of the challenges imposed by the spectral characteristics of tissue which make the design of a commercially viable measurement system a formidable task. Thus, there is a substantial need for a commercially viable device which incorporates subsystems and methods with sufficient accuracy and precision to make clinically relevant determinations of biological attributes in human tissue. The present invention is primarily concerned with the optical probe, which is one of the system components that influence commercial viability of a non-invasive measurement system.
In U.S. Pat. No. 5,953,477, Wach et al. disclose embodiments of optical fiber treatments that serve to improve the efficiency of optical probes. The treatments include reflective surfaces coatings applied to fibers that have been ground or shaped to alter the light output or collection properties of the fiber at the sample interface. Wach et al. also disclose the application of optical filtering materials directly to the ends of the optical fibers at sample interface. All of the embodiments involve a central fiber surrounded by a circular arrangement of additional fibers with at least one having a shaped end or internally reflective surfaces to bend or steer the emitted or collected light paths from its longitudinal axis (e.g., the axis parallel to the optical fiber and perpendicular to the sample interface). None of the embodiments disclosed in the present invention involve circular arrangements at the sample interface, shaping the ends of any fibers, or internally reflective surfaces to steer or bend light paths.
In U.S. Pat. No. 6,006,001 Alfano et al. disclose embodiments of optical probes suitable for endoscopy. All disclosed embodiments are comprised of illumination and collection fibers encased in a tubular structure and include a narrow band filter between the illumination and collection fibers. None of the embodiments disclosed in the present invention involve tubular encasing structures or narrow band filters.
In U.S. Pat. No. 6,219,565 Cupp et al. discloses optical probes for measuring glucose. All independent claims are limited to glucose and ring geometries (illumination fibers surround each collection fiber in a circular pattern). None of the embodiments of the present invention involve ring illumination/collection geometries.
In U.S. Pat. No. 6,411,373, Garside et al. disclose fiber optic illumination and detection patterns for use in spectroscopic analysis. They disclose a design process for determining the illumination-detection pattern at the sample interface. The ratio of the illumination to detector fibers in the disclosed embodiments is restricted by the size of the fiber bundle at the detector. The embodiments of the present invention are not subject to this restriction. Furthermore, Garside et al. disclose optical probe embodiments incorporating hex-packed fibers. None of the embodiments disclosed in the present invention involve hex-packed optical fibers at the sample interface. Garside et al, further disclose a design method that states “fabrication constraints should be ignored whenever possible”, and as such, is a starkly contrasting approach to that of the present invention.
In U.S. Pat. No. 6,678,541, Durkin et al. disclose optical probe geometries for measuring optical properties, such as the scattering coefficient of a sample. A single illumination channel is used to sequentially measure the sample at multiple collection channels at different separations relative to the illumination channel. A function relating the change in signal to illumination/collection separation is then used to determine the optical property of interest. No embodiments of the present invention involve determining properties by examining signals as a function of illumination/collection separation.
In U.S. Pat. No. 6,870,620, Faupel et al. disclose optical probe embodiments that are predominantly suited to fluorescence spectroscopy. All of the embodiments involve translating, rotating, or repositioning the optical probe during a measurement or a sample interface surface that conforms to the shape of the sample being measured. None of the embodiments of the present invention involve rotating, translating, or otherwise moving the optical probe. Furthermore, none of the embodiments of the present invention involve sample interfaces that conform to the sample shape. In the embodiments of the present invention, the sample interface is polished flat.
In U.S. Pat. No. 7,136,076, Marbach discloses multi-channel optical probes for cancelling out surface effects of samples. Marbach does not disclose the advantages of or motivations for using multi-channel optical probes other than compensating for surface effects. For example, inducing multiple pathlengths through a sample using a multi-channel probe can provide insight into the pathlengths of each channel that might be obfuscated if only a single channel measurement were performed. Furthermore, all independent claims incorporate the explicit step of using algorithms or equations to process the measured channels in order to cancel surface effects. None of the embodiments of the present invention involve algorithms or equations to explicitly cancel surface effects.